Effect of silymarin on gluconeogenesis and lactate production in exercising rats. Authors: Eun-Ju Choi, Eun-Kyung Kim, Nam Ho Jeoung, and Sang-Hyun Kim Journal: Food Sci. Biotechnol. 25(S): 119-124 (2016) DOI 10.1007/s10068-016-0108-5 Abstract: In this study, we investigated the effects of silymarin (SM) on gluconeogenesis during exercise in rats. After 4 weeks of exercise, blood samples, liver, and skeletal muscle tissues were collected, and the levels of triglycerides (TG), lactate, peroxisome proliferator activated receptor gamma (PPARγ), phosphoenol pyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase 4 (PDK4), and phosphorylated 5-AMP activated protein kinase (AMPK) were measured. The TG and lactate level of the serum were reduced. In addition, the expression of Akt, PEPCK, and PPARγ in liver was decreased as well as the expression of AMPK in muscle. On the contrary, the level of PDK4 in muscle was increased. These results showed that that administration of SM ameliorated exerciseinduced gluconeogenesis and β-oxidation through the regulation of PPARγ, PEPCK, and PDK4. Thus, intake of SM during exercise may improve endurance by modulating of the metabolism of glucose, lipids, and lactate. https://link.springer.com/article/10.1007/s10068-016-0108-5 Eye-catching quotes from the paper: - "In this study, we examined, for the first time, the effects of SM administration on hepatic gluconeogenesis and lactate production in the skeletal muscles of exercising rats. Our findings clearly showed that SM had beneficial effects similar to exercise endurance in exercise-trained rats. Thus, SM may represent a novel supplement for improving physical performance and activity." - "[T]he observed decreases in serum lactate by SM administration during exercise indicated that SM administration improved exercise endurance due to reduced accumulation of lactate in skeletal muscles. The lactate produced from skeletal muscle may be used for hepatic gluconeogenesis to provide glucose to peripheral tissues during exercise." - "In summary, we showed that long-term treatment with SM combined with low-intensity exercise increased the utilization of lactate for gluconeogenesis via induction of the PPARγ-PEPCK signaling pathway in the liver, resulting in lower lactate levels and triglyceride in the blood." (All highlighting mine.) I'm no medical professional, but this study seems to imply that Silymarin (SM) might be able to reduce lactate levels which, it is thought, could be (partially) responsible for the muscle aches and brain fog so common in ME/CFS. Might be worth a shot!